1. Field of the Invention
The present invention relates generally to osteoblast cells and their role in bone formation. More specifically, the invention relates to the identification and isolation of genes encoding osteoblast cell proteins required for bone formation.
2. Description of Related Art
Bone formation is a carefully controlled developmental process involving morphogen-mediated patterning signals that define areas of initial mesenchyme condensation followed by induction of cell-specific differentiation programs to produce chondrocytes and osteoblasts. Positional information is conveyed via gradients of molecules, such as Sonic Hedgehog, that are released from cells within a particular morphogenic field together with region-specific patterns of hox gene expression. These, in turn, regulate the localized production of bone morphogenetic proteins and related molecules which initiate chondrocyte- and osteoblast- specific differentiation programs. Differentiation requires the initial commitment of mesenchymal stem cells to a given lineage, followed by induction of tissue-specific patterns of gene expression. Considerable information about the control of osteoblast-specific gene expression has come from analysis of the promoter regions of genes encoding proteins like osteocalcin that are selectively expresses in bone. Both general and tissue-specific transcription factors control this promoter. Osf2/Cbfa1, the first osteoblast specific transcription factor to be identified, is expressed early in the osteoblast lineage and interacts with specific DNA sequences in the osteocalcin promoter essential for its selective expression in osteoblasts. (Franceschi 1999). Cbfa1 is needed for osteoclast differentiation.
The reduced bone mineral density (BMD) observed in osteoporosis results, in part, from reduced activity of bone-forming osteoblasts (Jackson 2000). The identification of transcription factors that participate in the cell differentiation process has been beneficial in developing treatment protocols for osteoporosis. It is likely that other transcription factors participate in the differentiation process as well. It would be beneficial to identify a master transcription for the development of agents to enhance bone formation in treatment of bone diseases such as osteoporosis.